Selected Fellows Call 2016

Below you will find an overview of the proposals of the successful candidates of the 2016 call by alphabetical order.

To explore the scientific outputs of our fellows, please search them on Infoscience

Floquet Topological Insulator of magnon

Laboratory of Nanoscale Magnetic Materials and Magnonics (LMGN)

©Kyongmo An

The power consumption in conventional information technology such as CPU and memory devices has increased rapidly for the last few decades. As the size of the devices becomes smaller and the density becomes higher, the increased heating and leakage currents limit advancements in performance. This issue has raised demands for alternative ways of information transfer. Instead of the charge of an electron, the spin of an electron can be used to store, process, and transmit information. If spins get excited in magnetic materials, they form waves which can be useful for information processing at low power consumption and with small foot print.

In this project, we employ magnetic artificial crystals to obtain the desired transport properties of spin waves, in a similar way that photonic crystals tailor band structures for electromagnetic waves. In magnonic crystals, topologically protected spin wave edge modes can emerge upon driving the system with a time-periodic magnetic field. The generated state is robust and immune to disorder, similar to charge carriers in a superconductor. By creating an artificial magnetic crystal with both spatial and temporal modulation, we aim at obtaining an unprecedented flexibility in controlling the spin wave band structure and topologically protected edge modes.

(Start date of fellowship: 1 April 2017)

©Kyongmo An
Fig. 1 Illustration of spin wave propagating on a topological surface.

Optospintronics in Graphene\\WS2 Van der Waals Heterostructures

Laboratory of Nanoscale Electronics and Structures (LANES)

See publications

©Ahmet Avsar

Electron spin is an important state variable and has been considered as complimenting or even replacing the charge degree of freedom in current information storage and logic devices. With respect to the material selection for long distance spin communication, two-dimensional graphene is the most appealing material as it exhibits the longest spin relaxation length. However, these values are still orders of magnitude smaller than the theoretical estimations mostly due to spin dependent scattering at the contact/graphene interfaces. Nondestructive optical spin injection schemes are expected solve this major issue. However, the absence of sufficient spin-orbit coupling and weak optical absorption of graphene makes its implementation impossible.

In this proposal, we aim optical spin injection into graphene by bringing it in a close proximity with monolayer WSe2 crystal. Application of circularly polarized light will activate the spin-polarized charge carriers in WSe2 layer due to its spin-coupled valley-selective absorption. Next, these generated carriers will diffuse into the superjacent graphene layer, transport, and are finally electrically detected in a non-local geometry. With this project, we aim accessing the intrinsic spin transport properties of graphene by creating a van der Waals heterostructure which will have a major impact on the prospect of 2D spintronics.

(Start date of fellowship: 1 June 2017)

©Ahmet Avsar
Figure: Optical spin injection into graphene. A circularly-polarized light activates the spin-polarized charge carriers in the WS2 layer. This generated spin current tunnels into the graphene layer where it can be detected by the detector electrode having a BN tunnel barrier underneath.

On-chip biolaser platform for single cell single molecule analysis

Prof. Aeppli – Group UPAEPPLI

See publications

©Joe Bailey

I am currently working on the study of coherent spinwave (magnon) behaviour in nanoscale magnetic devices. Spinwaves, or magnons in the quasiparticle description, are the propagation of disturbances to local magnetic ordering.

Using such a mechanism for the transfer of information has a number of advantages over conventional electronics: the propagation does not involve the transport of charge and therefore does not suffer from ohmic losses, furthermore there is significant spatial compression of signals for a given frequency allowing for more compact devices. I am currently researching coherent behaviour in such systems, analogous to lasing in optical materials, using x-ray magnetic circular dichroism (XMCD) synchrotron based techniques.

(Start date of fellowship: 1 August 2017)

©Joe Bailey
Top: Schematics showing spinwave. Magnetic moments (red spheres) precess with a periodic phase difference with wavelength λ. Bottom: Typical three level system common to lasers. The system is excited to state E2 by an external pump, with a fast non radiative decay to an intermediate state E1, the decay from this state to E0 via stimulated emission results in an amplification of an original seed input.

Dynamic dissection of centriole assembly mechanisms

Prof. Gönczy – Group UPGON

See publications

©Niccolo Banterle

The ultimate aim of my project is to unravel the mechanisms governing assembly of the centriole. The centriole is an organelle critical for fundamental cellular processes such as polarity, sensing, motility and division. Accordingly, defects in centriole assembly and number regulation contribute to several pathological conditions, including ciliopathies, microcephaly and cancer. In most species, the centriole assembles around a cartwheel ~100nm high comprising several superimposed rings of nine homodimers of the SAS-6 protein and probably associated components.

To understand how the centriole organelle assembles, it is thus crucial to decipher the mechanisms governing cartwheel formation. However, the dynamics of SAS-6 ring assembly and stacking, as well as the exact contribution of molecular partners of SAS-6 to these processes is not known. I utilize high-speed atomic force microscopy (AFM) to monitor the assembly kinetics of SAS-6 in real time and thus determine the relevant kinetic constants for ring formation and stacking (collaboration with the Fantner lab).

Moreover, I am determining the exact contribution to the assembly reaction of the SAS-6 molecular partners. I am also conducting high-throughput super-resolution STORM microscopy of SAS-6 associated proteins in purified human centrioles to reconstruct a detailed map of human centrioles (collaboration with the Manley lab).

(Start date of fellowship: 1 March 2017)

©Guichard P, Hachet V, Majubu N, Neves A, Demurtas D, et al. 2013. Native architecture of the centriole proximal region reveals features underlying its 9-fold radial symmetry. Curr. Biol. 23(17): 1620–28
The goal of my project is to decipher centriole assembly mechanisms (top panel, blue components represent SAS-6 proteins) using notably high speed atomic force microscopy (bottom left) and high throughput super resolution imaging (bottom right).

Aerolysin pores for single-molecule analysis

Prof. Dal Peraro – Group UPDALPE

See publications

©Chan Cao

Biological nanopores are emerging as powerful single-molecule devices to study various biomolecules and their interactions. Depending on the fluctuations of ion current as a molecule is transported through the nanopore, the properties of the molecule can be read out in real-time, such as its composition, structure and conformation. The great prospect of nanopore-based techniques using natural self-assembling protein complexes has spurred tremendous expectations and research efforts in the development of novel nanoscale pore materials.

I have recently discovered that aerolysin, a pore-forming toxin produced by Aeromonas sp., exhibits an unexceptional sensitivity for the detection of single oligonucleotides both in current separation (17%) and duration (~2.0 ms/nucleotide), which already falls within the optimal reading rate for DNA sensing. However, the lack of structural characterization of the pore conformations has so far hindered a deep molecular understanding of these unexpected features. Relying on recent high-resolution cryo-electron microscopy pore structures, the goal of this project is to understand the factors that influence the sensitivity of aerolysin when used as a single-molecule sensor. I will dissect the properties of aerolysin pores integrating molecular modelling and simulations with single-channel recording, with the ultimate aim of engineering nanopores with enhanced efficiency as nanosensor devices.

(Start date of fellowship: 1 May 2017)

©Matteo Dal Peraro
Johannes Broichhagen project picture
Schematic representation of the aerolysin nanopore system and proposed molecular dynamic simulations.

The Coordination Chemistry of Nitrous Oxide Derived Ligands

Laboratory of Supramolecular Chemistry (LCS)

See publications

©Kay Severin

Nitrous Oxide (N2O), more commonly known as laughing gas, is a greenhouse gas 300 times more damaging than carbon dioxide. Whilst the latter has received considerable attention over the last few decades, research on the use and derivatization of nitrous oxide is surprisingly lacking. To date there are few chemical applications for its use, primarily due to the difficulty in activating the molecule towards further reactivity. There are two potential avenues to using nitrous oxide, either exploiting it as an oxidant or by reacting the molecule with other simple, but reactive, complexes to make value-added products. This second route is being explored in this project.

My research involves taking nitrous oxide, incorporating it into a molecular scaffold (called a ligand) which can then be bound to a metal centre to make a nitrous oxide derived organometallic complex. Organometallic complexes are the cornerstone of the chemical industry, with myriad applications. My primary interest is to make catalytically relevant species – i.e. those that can be used to speed up chemical reactions to make them economically viable. This research project will therefore provide a use for this as yet unexploited resource.

(Start date of fellowship: 1 March 2017)

©Mark Chadwick
Figure 1: The transformation of nitrous oxide derived organometallic complexes.

LRH-1: control of liver cancer growth through glutaminolysis and mTOR signaling

Schoonjans Group UPSCHOONJANS

See publications

©Dasa Demagny

Primary liver cancer is the second leading cause of cancer-related deaths worldwide, with current treatments being very limited. LRH-1 is a receptor in the cell nucleus, where it regulates the expression of various genes.

In this proposal, I propose to test the hypothesis that the nuclear receptor LRH-1 coordinates several key genes that are involved in the metabolism of glutamine – an amino acid to which liver cancer cells become addicted. I will test whether LRH-1 drives the development of liver tumours by helping cancer cells to convert glutamine into molecules that are directly needed for proliferation. If successful, this study could place LRH-1 as a new potential drug target to prevent the development of liver cancer.

(Start date of fellowship: 1 March 2016)

A flluorescence image of liver cells and the chemical structure of glutamine.

©K. Schoonjans/EPFL

Embodied carbon impacts of structural design in Switzerland

Structural Exploration Lab (SXL)

See publications

©Mary-Ann Staar

Whole life cycle emissions of buildings include not only operational carbon due to their use phase, but also embodied carbon due to the rest of their life cycle: material extraction, transport to the site, construction, and demolition. With feedback from a wide range of stakeholders – architects, structural engineers, policy makers, rating-scheme developers, this research presents an integrated design approach to reduce life cycle impacts of building structures.

First, data on material quantities and embodied carbon of existing buildings are collected from practitioners. The database of embodied Quantity outputs (deQo) is used to collect data through the Structural Engineers 2050 Commitment.

Second, the influence of structural systems on their life cycle impacts is studied, looking at tensile structures, compressive structures, trusses, shear walls and bending beams in the database. This analysis is performed in close collaboration with engineering firms to give insights on current structural design practice.

Third, new low carbon structural design alternatives are developed and tested against feasibility. The final goal is to offer low carbon guidelines for the building industry.

(Start date of fellowship: 1 August 2017)

©Catherine De Wolf
Results for the embodied carbon in different structural systems from the database of embodied Quantity outputs (deQo).

Computational Methods for Polynomial Financial Models and Complexity Reduction

Swiss Finance Institute

Core problems in finance, such as pricing, calibration, hedging, uncertainty quantification, intra-day risk monitoring and stress testing, require real-time evaluations. These evaluations are directly linked to financial decision-making. It is therefore imperative that they have suitable accuracy and performance guarantees and that their outputs allow for a clear and intuitive interpretation.

In order to advance the field of quantitative finance, I am developing efficient and rigorous data-based computational methods. Distinctive of my approach is to marry the explanatory force of stochastic financial modelling and numerical analysis to the potential of learning algorithms to solve high-dimensional non-linear problems. I combine the proven strengths from these three fields by deploying techniques from classical numerical analysis (partial differential equation, Fourier, and interpolation techniques, dynamic programming), complexity reduction (model order reduction, reduced basis methods, general empirical interpolation) and financial modelling (asset prices, fixed income, stochastic processes with jumps). Based on my expertise in mathematical finance and numerical and stochastic analysis, I am

  1. exploring new software and technologies for finance,
  2. developing new data-driven computational methods for finance,
  3. analysing these methods extensively theoretically and with numerical experiments,
  4. applying and implementing to real-world problems in the financial industry.

You can find more details and the list of my publications, on my homepage

Stereodynamics near absolute zero: merged beam studies of oriented molecules

Laboratory of Molecular Physical Chemistry (LCPM)

See publications

Trillions of collisions are taking place at any moment all around us. Collisions of a tennis racquet with a ball, collisions of snowflakes with our skin and even of air on our faces as we walk. These collisions are all rather high energy in that they occur between molecules with not insignificant amounts of internal energy. As we know, energy is partitioned into different modes such as rotation (how fast something is rotating) vibration (how much it is wiggling) and electronic energy. Of course, if there are two species colliding another important parameter is the orientations of the colliders, which direction are they spinning (left or right) and where is the vibration pointing (towards or away from the other molecule)? Depending on all these parameters is the scattering outcome. Is there a reaction? Does nothing happen? Do the scattered products tend to scatter into a particular direction or gain a certain amount of rotational energy? It is these questions that are of critical interest in stereodynamical studies.

As a system is cooled, very interesting things can happen to it and quantum phenomena come to the forefront of the system’s behavior. For instance, when helium is liquefied and cooled, it can overcome friction and climb against gravity! Other interesting effects can happen in collision systems, for instance the probabilities of scattering or reaction can drastically fall or increase by changing the system internal energy by only a miniscule amount. It is these collisions that we study in order to see if our best theoretical models can explain such drastic changes of the scattering outcome with accuracy and precision. By combining cold collisions with stereodynamics we hope to gain the most possible insight into the behavior of fundamental forces acting between individual molecules and learn to manipulate and control those forces to drive the reaction outcome in a particular direction of our choosing.

Molecular Layer Deposition of Ultrathin MOF membranes for Size-selective Separation

Gaznat Chair for advanced separations (LAS)

See publications

©Jing Zhao

Molecular separation membranes are of great importance owing to their potential to remarkably enhance the energy efficiency and reduce the cost of clean fuel production. Membrane process can significantly decrease the energy consumption compared with thermally-driven separation processes. However, polymer membranes suffer from a drastic trade-off between molecular flux and selectivity. To address this issue, it is imperative to develop a methodology to fabricate ultrathin molecular sieving membranes (MSMs), enabling precise separation with ultrahigh throughput.

Metal–organic frameworks (MOFs), which show regular crystalline lattices with highly tunable pore structures, are ideal starting materials to manufacture MSMs. Unfortunately, the fabrication of ultrathin, size-selective MOF membranes has remained elusive, mainly due to the limitations of the solvothermal technique. Herein, we propose to develop a general methodology called molecular layer deposition to fabricate ultrathin MOF membranes (few unit-cell thick) with unprecedented high flux and selectivity for molecule mixtures. This project is of great importance in that it will develop a general methodology to fabricate ultrathin MOF membranes, and pave the way to fabricate next-generation high-performance MSM at molecular scale level. We believe this methodology will open up a new avenue to fabricate ultrathin crystalline nanoporous films, which could find applications in a number of processes, thus addressing various environment and energy-related issues.

(Start date of fellowship: 1 April 2017)

Fabrication of MOF membrane using a molecular-layer-deposition method.

©Guangwei He

Restoration of voluntary motor control after severe contusion injury with neurorehabilitation in mice

Prof. Courtine – Group UPCOURTINE

©Claudia Kathe

Clinically complete spinal cord injury leads to permanent loss of motor function. Excitingly, spinal stimulations combined with neurorehabilitative training immediately restores will-powered control of completely paralyzed legs and improves long-term outcomes. The Courtine group has developed a new intervention that combines will-powered neurorehabilitation with electrochemical spinal stimulations for rodents with spinal cord injury.

I propose to first elucidate which ‘silent’ spared pathways may act as immediate relay pathways for will-power signals after severe contusions in mice during neurostimulation. I will use a combination of tracers to label and identify brain(stem) projections to the lumbar spinal cord, where the locomotor centre for the hindlimbs resides. I will prove these brain(stem) projections are required to rely motor cortex commands by silencing them with the chemogenetics, which should abolish any leg motor function.

Finally, I will address whether long-term lumbar spinal cord reactivation strengthens these motor control relay pathways, improves voluntary motor function and which neuroanatomical mechanisms underlie this plasticity. Taken together, these results will establish the causal relationship between circuit reorganisation of residual descending projections and voluntary motor control with electrochemical neurorehabilitation in severe spinal contusion injuries.

(Start date of fellowship: 1 March 2017)

©Claudia Kathe
Combining cortical optogenetic stimulation with electrochemical spinal stimulation. (A-C) Optic fibres are implanted over the hindlimb cortex in Thy1-ChR2 mice (B). Mice receive severe contusion injuries and lesion sites are 3D reconstructed; transverse sections are stained with astrocytic (GFAP) and neuronal markers (Nissl) (C). (D) Mice are trained and tested on the neurorehabilitative platform during electrochemical stimulation only and during combined optical and electrochemical stimulation. EMG recordings from hindlimb flexor and extensor muscles indicate combined stimulation immediately improve the locomotion pattern.

Breast cancer-on-a-chip: an in vivo like early platform integrated with electrochemical sensors for chemotherapeutic testing and cancer progression monitoring

Integrated Systems Laboratory (LSI)

See publications

©Tugba Kilic

The emergence of personalized medicine for cancer treatment calls for the development of novel strategies not only to design new generation chemotherapeutics, controlled/targeted drug delivery, but also to test drug candidates in an in-vivo-like platforms to bridge the gap between the currently used pre-clinical animal models and the human body. Therefore, there is an urgent demand for the development of human-based three-dimensional (3D) cancer models that precisely recapitulate the cancer microenvironment and functions of their counterparts in vivo.

To this end, the recently emerging organs-on-a-chip systems that combine advanced microfluidic technologies and tissue engineering approaches to simulate both the biology and physiology of the human organs have been emerged as a viable platform. These in vitro models also transformed into cancer-on-a-chip, tumor-on-a-chip systems to study the cancer microenvironment, progression and metastasis. However, assessment of these systems via in situ continual measurement of biomarker levels have not been achieved via microfluidics-based sensing modules.

Therefore, the goal of the present project is to design a breast cancer-on-a-chip with integrated electrochemical sensors for circulating miRNA and exosome detection to test efficacy of chemotherapeutics as represented in Figure.1.

(Start date of fellowship: 1 March 2017)

©Tugba Kilic
Figure 1 The state-of-the proposed research project: Breast cancer-on-a-chip platform integrated to multiplexed electrochemical sensors to monitor changes in exosomes and circulating miRNAs upon exposure to certain chemotherapeutics.

First-principles Simulations on 2D Materials: Towards Novel Hydrogen Evolution Electrocatalysts

Laboratory of theory and simulation of materials (THEOS)

See publications

©Francesco Nattino

Electrochemistry is one of the key enablers for a world based on sustainable energy – from solar energy harvesting, to storage and conversion. Hydrogen represents a well-known example of ‘clean’ energy carrier, as one could base on this molecule a fossil-fuel-free energy cycle. Ideally, one could produce H2 from the electrolysis of water and subsequently retrieve energy from it via fuel cells, with water as only by-product.

Computer simulations can provide an enormous contribution to the search for inexpensive and selective catalysts for the electrosynthesis of hydrogen and other interesting fuels. By being parameter-free (‘from first-principles’) and therefore not material specific, quantum mechanical methods can not only help in understanding the working mechanism of current catalysts, but they also allow for a fast, cheap and safe screening of large libraries of potentially interesting materials for desired applications.

In this project, I will apply novel approaches to accurately model electrochemical interfaces within first-principles simulations (see Figure 1). I will then use these tools to explore the stability and the catalytic activity of present and novel materials in order to identify optimal catalysts for target reaction processes.

(Start date of fellowship: 1 July 2017)

©Francesco Nattino
Figure 1. The solvent and the electrolyte (left) constitute conceptual challenges in the first-principles modelling of electrochemical interfaces. The strategy that will be adopted in this project consists in accounting for their presence through a dielectric medium and a diffuse ionic charge density, respectively (right).

3D numerical modeling of hydraulic fracture propagation

Geo-energy Laboratory – Gaznat Chair on Geo-energy (GEL)

See publications


The main goal of the project is development of a new computational code for simulation of the growth of three-dimensional hydraulic fractures based on a fully three-dimensional solid-fluid model coupled to a fracture propagation scheme.

In this project, special care will be taken to account for the fracture front instability and segmentation under mixed loading mode, which, to our knowledge, is not properly handled numerically by any computer code for hydraulic fracture growth developed to date. The complete numerical code will be based on a 3D boundary element scheme with high order approximation to describe the elastic deformation of the rock and a finite volume (or, alternatively, a finite element) scheme to model the fluid flow in the newly created fracture.

Anticipating the need for large-scale computations, special care will be taken to accelerate and parallelize the code. The code will be released under an open-source license and made available to other researchers via a dedicated website.

(Start date of fellowship: 1 June 2017)

©Society of Petroleum Engineers
An example of near-wellbore tortuosity of a hydraulic fracture in a laboratory experiment.

Role of extracellular matrix receptor CMG2 in mesenchymal cell fate determination

The extracellular matrix (ECM) plays crucial role controlling cell behavior, survival and differentiation. It serves environment for cell communication and migration, and regulates tissue remodeling. The project is focused on the role of ECM receptor, capillary morphogenesis gene 2 (CMG2), in determining cell fate.

Loss of CMG2 function causes Hyaline Fibromatosis syndrome. This disabling genetic disorder is characterized by accumulation of ECM in organs, gingival hypertrophy, subcutaneous nodules, osteolytic bone defects and joint contractures as well as lethality in the severest juvenile form. Physiological function of CMG2 in adult organism as well as molecular mechanisms of Hyaline Fibromatosis syndrome development are not clear.

The proposal is aimed at investigation of a novel player in cell-to-ECM interaction and mechanism affecting lineage commitment of mesenchymal stem cells (MSCs) that could contribute to understanding of HFS symptoms. Understanding cues for MSCs lineage commitment is essential for their successful application in regenerative medicine.

(Start date of fellowship: 1 August 2017)

©Olha Novokhatska
Left panel: Effect of ECM stiffness on MSCs differentiation. Right panel: Mouse adipocytes differentiated in vitro: lipid droplets in green, nuclei in blue.

AQuViDa – Approximate Queries over Virtualized Data

Data-Intensive Applications and Systems Laboratory (DIAS)

© Odysseas Papapetrou

The project focused on developing a self-tuning engine for approximate query processing over big data. The mainstream approach on big data analytics involves building huge clusters and relying on distributed filesystems and massively parallel processing platforms like Hadoop HDFS and Spark, for storing and analyzing the data. However, this approach is typically inaccessible to SMEs, due to the significant monetary cost.

A cost-sensitive approach relies on approximation algorithms to facilitate near-real-time approximate analytics with traditional hardware. Existing systems relying on approximation algorithms are restricted to relational data, require continuous tuning of the query engine and – to a certain extend – assume knowledge of the underlying techniques (e.g., the available synopses and the accompanying theoretical results). The project targeted to a query engine that: (a) takes all decisions independently, and transparently from the user, (b) exploits data virtualization in order to facilitate seamless analysis of heterogeneous data.

The first part of the project led to Taster, a fully self-tuning scalable query engine that improves the state-of-the-art [OPAA19]. Part of this improvement is attributed to the utilization of a richer set of synopsis types (different types of sketches and samples) that are more efficient on answering some queries. The architecture of Taster is summarized in Fig. 1. We also explored how hardware accelerators can be used to construct synopses [CPP+19], and proposed efficient implementations of ECM-sketches over FPGAs (see Fig. 2 for the architecture). Our fastest implementation is able to sustain 150 Million updates per second.

Due to accepting a new job, I interrupted my fellowship in mid 2018, before starting to work on the second part of the project.

Figure 1: Architecture of Taster.
Figure 2: FPGA architecture for maintaining an ECM-sketch.


Publications resulting from the fellowship:

[OPAA19] Matthaios Olma, Odysseas Papapetrou, Raja Appuswamy, Anastasia Ailamaki. Taster: Self-Tuning, Elastic and Online Approximate Query Processing. 2019 IEEE 35th International Conference on Data Engineering (ICDE).

[CPP+19] Grigorios Chrysos, Odysseas Papapetrou, Dionisios Pnevmatikatos, Apostolos Dollas, Minos Garofalakis. Data stream statistics over sliding windows: How to summarize 150 Million updates per second on a single node. 2019 29th International Conference on Field Programmable Logic and Applications (FPL). 


(Start date of fellowship: 01.01.2018)

PROGRESS – Prospection and Production of Geotherman Reservoir

Laboratory of Experimental Rock Mechanics (LEMR)

See publications

©Lucas Pimienta

Geothermal energy, using the Earth internal temperature as an energy source, is a critical technology to mitigate global warming. The procedure is to heat up a circulating fluid in a geological reservoir. Depending on the fluid’s circulation rate and temperature, the reservoir will be deemed as profitable. Properly assessing this geothermal efficiency requires knowing precisely the reservoir initial temperature, and the reservoir rocks’ properties responsible for a sustainable flow and heating rate of the fluid during its propagation within the reservoir.

However, none of those properties can yet be precisely measured or predicted. Furthermore, when increasing the fluid’s flow rate, induced seismicity and, in some cases, earthquakes were shown to occur. The aim of this project is to tackle these two issues, which constitute major technological barriers for profitable and sustainable geothermal energy field exploitation.

(Start date of fellowship: 1 March 2017)

©Lucas Pimienta
Proposed experiments.

Development of Mirror-Image Monobodies as Novel Cancer Therapeutics

Prof. Hantschel – Group UPHAN

See publications

©Timothy Reichart

Targeted monoclonal antibody therapies have transformed the landscape of clinical cancer care, in the best cases transforming previous fatal diseases into ones managed through chronic treatment. However, antibody therapies have significant downsides, including potentially serious side effects such as severe immune responses that require stopping treatment. To address the problem presented by therapeutic protein immunogenicity and allow long-term therapy for a greater percentage of patients, we are developing targeted cancer therapeutics using mirror image proteins. Consisting of the mirror image component amino acids, mirror image proteins are much more stabile than natural proteins, and are not immunogenic.

Identifying mirror image protein therapeutics is difficult as there is no direct way to screen them. To get around this, we synthesize the mirror image target, use that to screen natural proteins that bind the target, then take advantage of symmetry to know that the mirror image protein therapeutic binds the natural target in exactly the same way. We are currently using these techniques to try to identify protein therapies against different tumor cell markers and cancer immunotherapy targets.

(Start date of fellowship: 1 May 2017)

©Timothy Reichart
Overview of the development of mirror-image protein therapeutics.

Next-generation interconnection and packaging technologies for biomedical devices

Foundation Bertarelli Chair in Neuroprosthetic Technology (LSBI)

See publications

©Giuseppe Schiavone

Soft bioelectronics is an emerging field that uses soft materials, stretchable metallisation, and embedded electronic devices to manufacture highly conformal electronic circuits. This combination is particularly suited for applications at the interface with biological tissue, as the soft materials employed offer superior long-term biointegration compared to conventional silicon-based electronics.

At present, the integration of soft devices with external electronics is only achieved via serial interconnection techniques, where solder material is applied on dedicated pads to form individual electrical connections. This constitutes a clear manufacturing bottleneck for complex devices, and it highlights an unmet need for enhanced techniques.

My project tackles this specific challenge and aims at developing scalable and batch-process packaging technologies applied to soft bioelectronic devices, by leveraging the use of ad-hoc materials, such as anisotropic conductive composites and stretchable conductive fibres. My main objectives are to demonstrate batch-packaged soft microelectrode arrays functionally deployed in-vivo, and to test their reliability against mechanical, electrochemical and biological wear.

The research outcomes will enable a higher level of integration for implantable bioelectronics by shrinking the interconnection volume and cost. The technologies developed will however also be relevant for non-implanted systems where soft materials are desirable, such as artificial skins or wearable electronics.

(Start date of fellowship: 1 July 2017)

a) A soft e-dura microelectrode array designed for rat spinal cord implantation b) Detail of the interface between the in-plane microtechnology and the discrete wires c) Envisaged switch to batch-interconnection technology for improved system integration

Cosmic magnetic fields and the reionization of the Universe

Laboratory of Astrophysics (LASTRO)

©Jennifer Schober

More than 99% of the normal (baryonic) matter of our Universe is ionized. As a result, Lorentz forces from magnetic fields, which are observed from the smallest astronomical scales, like planets and stars, up to galaxies and galaxy clusters, can affect astrophysical flows.

In this project we will study the origin of cosmic magnetic fields in the early Universe, when it was less than a second old and extremely hot. At these high energies quantum effects related to the chirality of particles (fermions) can play a significant role in amplifying magnetic fields. To gain detailed understanding on this novel mechanism, we will perform high-resolution numerical simulations of relativistic plasmas on supercomputers.

If these primordial magnetic fields are strong they can influence the subsequent evolution of the Universe. In particular, the seeds of cosmic structure, tiny density fluctuations from the Big Bang, can be slightly modified, leading to a suppression of the formation of small galaxies. One main question addressed in this project is whether these processes can influence reionization, the epoch between 150 and 1’000 million years after the Big Bang when the first galaxies and quasars ionized the intergalactic medium making the Universe transparent at ultraviolet wavelength.

(Start date of fellowship: 1 August 2017)

©NASA/ESA & Jennifer Schober
Astrophysical flows are studied by solving a set of coupled partial-differential equations in high-resolution numerical simulations, as illustrated here by the example of the velocity field in a turbulent, relativistic, and magnetized plasma.

Role of concurrent genomics lesions in follicular lymphoma development and progression

Prof. Oricchio – Group UPORICCHIO

See publications

©Stephanie Sungalee

Follicular lymphoma (FL) is the second most common form of indolent B-cell malignancies, accounting for 20-30% of all cases. Most patients have a slowly progressing form of the tumor but up to 40% of the cases transform into an aggressive form of lymphoma, transformed-FL with early death within one year. Despite indisputable progress resulting from combined chemo- and immunotherapy, FL remains virtually incurable. The genetic hallmark of FL is the BCL2/IGH translocation, present in more than 85% of the tumors, which increases the expression of the anti-apoptotic protein Bcl2. While being a critical early event in the natural history of FL, the translocation remains insufficient to trigger lymphomas and further driving genetic alterations are required to induce lymphomagenesis and transformation.

The present project aims at identifying the complementary hits leading to lymphoma. We propose to perform a bioinformatics analysis to identify recurrent lesions in FL. We will then mimic the lesions in vivo and in vitro to evaluate their functional impact in the initiation and development of FL. Elucidating the role of those secondary driving events in the initiation and progression of FL may reveal new targets for therapy.

(Start date of fellowship: 1 August 2017)

©Stephanie Sungalee and Elisa Oricchio
Our aim is to identify the complementary hits leading to Follicular Lymphoma (FL). We propose to perform a bioinformatics analysis to identify recurrent DNA alterations in the tumors from patients and mimic the lesions in vivo and in vitro to evaluate their functional impact in the initiation and development of FL.

Single-cell studies of host-pathogen interactions

Prof. McKinney – Group UPKIN

See publications

©Alberto Ravagnin

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a major cause of global morbidity and mortality. One of the secrets of this pathogen’s success is its ability to adapt to the lung immune defence mechanisms and persist for the lifetime of the host. At the onset of the infection, Mtb is internalized by alveolar macrophages residing within the lungs. The outcomes of these early interactions define the subsequent course of the infection. Recent studies have shown that marked cell-to-cell differences exist within genetically homogeneous populations of Mtb. This “phenotypic heterogeneity” is amplified during infection, which may favour the survival of subpopulations of cells during periods of stress imposed by host immune defences.

The aim of this project is to investigate the origins and consequences of cell-to-cell phenotypic heterogeneity in the interactions between macrophages and Mtb. Towards this goal, we have constructed a novel microfluidic platform for long-term time-lapse microscopy of Mtb internalized within macrophages. Our platform permits the simultaneous trapping and microscopic imaging of hundreds of infected host cells over long periods of time. Fluorescent markers will be used to study the physiology of individual host and bacterial cells. This approach will yield new insights into fundamental questions about tuberculosis pathogenesis and the heterogeneous responses of individual intracellular bacteria to antibiotic therapy.

(Start date of fellowship: 1 August 2017)

©Chiara Toniolo & Matthieu Delincé
A) Schematic representation of the proposed experimental approach used to investigate cell-to-cell phenotypic heterogeneity in the interactions between macrophages and Mtb. B) Murine macrophage (highlighted in white) infected with fluorescent Mtb-GFP inside a circular chamber in the microfluidic device.

Photoactive Frameworks as Smart Porous Materials (SmartPorous)

Laboratory for Functional Inorganic Materials (LFIM)

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©Olga Trukhina

Metal organic frameworks (MOFs) are the forefront smart porous materials with unprecedented surface areas and surface chemistry becoming extremely promising for gas separation, gas storage and catalysis (Figure-left). MOFs comprising metalloporphyrins are of particular interest due to the ubiquitous role of these macrocycles in biological processes, ranging from light-harvesting (e.g., chlorophylls) to oxygen and CO2 transport and regulation (e.g., hemoglobin). While the synthesis of porphyrin-based MOFs has recently garnered much interest, their photocatalytic behavior has been poorly explored and mostly restricted to the oxidation of organics.

The “SmartPorous” project pursues the main objective of creating photoactive porous frameworks for a variety of environmental applications. The straightforward method of assembling of MOFs in a modular way coupled with the dynamic nature of the porphyrinoid-based photoactive molecular struts, together constitute a bottom-up approach that will provide us with the key to access and engineer a wide range of frameworks with desirable properties to impact the field of heterogeneous photocatalysis for energy conversion (Figure-right), chemosensor technology and water purification.

(Start date of fellowship: 1 April 2017)

©Olga Trukhina
A scope of environmental applications (left), and an example of photoactive framework for small molecule conversion (right).

Quantum self-organized criticality and nonequilibrium light localization

Bionanophotonic Systems Laboratory (BIOS)

©Kosmas Tsakmakidis

The astonishingly high speed of light is a real asset for modern optical-fiber networks, enabling real-time communications from one side of the Earth to the other. However, there are nowadays many important applications for which we would also like to ‘trap’ and ‘localize’ light in order to increase its interaction with matter.

Potential applications include ultrafast lasers requiring strong nonlinear light-matter interactions, or photovoltaics and light harvesting devices where light should not pass through the material quickly so that it can be efficiently absorbed and converted into electricity. Another application is for optical bio-sensing and diagnostic devises, in which light is used to identify and trace various chemical elements and should thus interact strongly with these elements.

The objective of this project is to introduce and thoroughly analyze a fundamentally new way of spatially localizing light, not aided by standard cavity (resonator) effects, but instead exhibiting a, so called, ‘phase transition’ which is a thermodynamically new ‘phase’ or state of light to localization. This new type of critical (in the statistical-physics meaning) light behavior will be enhanced and controlled by quantum effects, such as the quantum vacuum fluctuations, will exhibit self-organization and adaptation, while also remaining unharmed by such deleterious effects as dissipative losses, fluctuations and nonlinear interactions.

(Start date of fellowship: 1 August 2017)

©Kosmas Tsakmakidis
Quantum-coherently controlled nonequilibrium light localization in a longitudinally-uniform plasmonic heterostructure.

©Kosmas Tsakmakidis

Synthetic organic chemistry with nitrous oxide

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©Kay Severin

Nitrous oxide (N2O) is a strong greenhouse gas, roughly 300 times worse than carbon dioxide. It is a byproduct of several industrial and agricultural processes and released into the atmosphere.

N2O is very inert, and as a consequence, it can only be used in a small number of chemical methods. These methods have severe chemical limitations. The research I am undertaking aims to find new procedures to use N2O as a chemical building block in organic chemistry. By screening novel nucleophiles I aim to develop procedures that allow for the synthesis of chemicals with added value. Examples of target structures include photoswitches and dyes. This way we hope to provide options to industry to reuse N2O instead of releasing it in our atmosphere.

(Start date of fellowship: 1 March 2017)

©Tim Wezeman
Development of novel strategies to covalently capture nitrous oxide.

Anticorrosive Carbon Monolayer Coatings with Tailored Tribology

Laboratory of Macromolecular and Organic Materials (LMOM)

©Reuben Yeo

The development of novel nanocoatings with superior corrosion protection and wear resistance is highly relevant for many advanced engineering applications. Carbon-based nanocoatings are favorable candidates because they are atomically dense and demonstrate excellent tribological properties. However, their broader application is limited by fabrication processes that are expensive and difficult to scale to large areas and mass production.

The proposed project aims to combine the advantages of carbon nanocoatings with a simple procedure for their fabrication: based on the crosslinking of self-assembled monolayers (SAMs) formed from reactive surfactants in solution. To this end, SAMs of reactive carbon-rich surfactants will be converted into functional carbon monolayer coatings by UV irradiation or thermal annealing. Furthermore, by employing surfactant molecules with different chemical functionalities as building blocks for the SAMs, we can obtain carbon monolayer coatings that possess specific binding to the substrate and tailored surface properties for enhanced tribology.

In the course of this project, we seek to gain a better understanding of the self-assembly of these surfactants on solid substrates, the mechanism of the carbonization reaction, and the structure-property relationships of the carbonized monolayer coatings at different length scales.

(Start date of fellowship: 1 March 2017)

©LMOM group
Self-assembly of reactive hexayne amphiphiles with different anchor groups A and different terminal functional groups X on selected inorganic substrates to yield well-defined SAMs, which could be converted into atomically dense carbon monolayer coatings with specific binding to the substrate and tailored surface chemistry.